Dear NONMEM users,
I have tried to study the pk profiles of a drug after multiple oral dosage regimen of 500mg every 12hr. The estimation process was well performed with the first dose (only) using Weibull function. but if i apply the same control file to the whole data (ie, single dose and multiple doses), it does not work any more. I can not detect my error. Could any one tell me where is it? neither first order nor Mich.-Menten models fitted the data like weibull model.
thank you very much in advance for your response.
sincerely yours
Abduljalil
$SUBROUTINES ADVAN6 TRANS1 TOL=3
$MODEL
COMP=(DEPOT,DEFDOSE)
COMP=(CENTRAL,DEFOBS)
$PK
CL=THETA(1)*EXP(ETA(1))
V=THETA(2)*EXP(ETA(2))
BETA=THETA(3)*EXP(ETA(3))
ALPHA=THETA(4)*EXP(ETA(4))
K=CL/V
S1=1
S2=V
$ERROR
DEL=0
IF(F.EQ.0) DEL=0.001
W=F
IPRED=F
IRES=DV-IPRED
IWRES=IRES/(W+DEL)
Y=F+EPS(1)
$DES
DADT(1)=-A(1)*(BETA/ALPHA)*((TIME/ALPHA)**(BETA-1))*EXP(-(TIME/ALPHA)**BETA)
DADT(2)=-DADT(1)-A(2)*K
$THETA
(0.01,17,80);
(10,115,900);
(0.1,2.2,30)
(0.1,2.6,30)
(0.001,2)
(0.001,1)
$OMEGA
0.1 0.2 0.08 0.2
$SIGMA
0.2
$EST METHOD=1 INTER PRINT=5 NOABORT MAXEVAL=9999
Weibull distribution
Dear Abduljalil,
I am not an expert on using the Weibull distribution for drug
absorption, but I suspect that the value of TIME in the equation for
DADT(1) should represent the elapsed time since the most recent dose.
For example, if dosing occurs at 0, 24, and 48 hours, then the
observation at 25 hours after the start of the study (ie, 1 hour after
the most recent dose) should use TIME=1 hour in the equation for
DADT(1). However, I suspect that TIME=25 hours is being used in the
current problem.
Good luck,
Steve
Quoted reply history
-----Original Message-----
From: [EMAIL PROTECTED] [mailto:[EMAIL PROTECTED]
On Behalf Of Khaled Mohammed Abduljalil
Sent: Wednesday, April 11, 2007 9:15 AM
To: [email protected]
Subject: [NMusers] Weibull distribution
Dear NONMEM users,
I have tried to study the pk profiles of a drug after
multiple oral dosage regimen of 500mg every 12hr. The
estimation process was well performed with the first dose
(only) using Weibull function. but if i apply the same
control file to the whole data (ie, single dose and
multiple doses), it does not work any more. I can not
detect my error. Could any one tell me where is it?
neither first order nor Mich.-Menten models fitted the
data like weibull model.
thank you very much in advance for your response.
sincerely yours
Abduljalil
$SUBROUTINES ADVAN6 TRANS1 TOL=3
$MODEL
COMP=(DEPOT,DEFDOSE)
COMP=(CENTRAL,DEFOBS)
$PK
CL=THETA(1)*EXP(ETA(1))
V=THETA(2)*EXP(ETA(2))
BETA=THETA(3)*EXP(ETA(3))
ALPHA=THETA(4)*EXP(ETA(4))
K=CL/V
S1=1
S2=V
$ERROR
DEL=0
IF(F.EQ.0) DEL=0.001
W=F
IPRED=F
IRES=DV-IPRED
IWRES=IRES/(W+DEL)
Y=F+EPS(1)
$DES
DADT(1)=-A(1)*(BETA/ALPHA)*((TIME/ALPHA)**(BETA-1))*EXP(-(TIME/ALPHA)**B
ETA)
DADT(2)=-DADT(1)-A(2)*K
$THETA
(0.01,17,80);
(10,115,900);
(0.1,2.2,30)
(0.1,2.6,30)
(0.001,2)
(0.001,1)
$OMEGA
0.1 0.2 0.08 0.2
$SIGMA
0.2
$EST METHOD=1 INTER PRINT=5 NOABORT MAXEVAL=9999
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The contents of this message are intended only for the use
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Steve makes a good point. You should be using the special variable T in $DES
not TIME. T is the instantaneous value of time used by the DE solver. TIME is
the time of the current record which the DE solver is attempting to move
towards to find a solution.
Try this for DADT(1):
DADT(1)=-A(1)*(BETA/ALPHA)*((T/ALPHA)**(BETA-1))*EXP(-(T/ALPHA)**BETA)
Nick
Steve Troy wrote:
>
> Dear Abduljalil,
>
> I am not an expert on using the Weibull distribution for drug
> absorption, but I suspect that the value of TIME in the equation for
> DADT(1) should represent the elapsed time since the most recent dose.
> For example, if dosing occurs at 0, 24, and 48 hours, then the
> observation at 25 hours after the start of the study (ie, 1 hour after
> the most recent dose) should use TIME=1 hour in the equation for
> DADT(1). However, I suspect that TIME=25 hours is being used in the
> current problem.
>
> Good luck,
>
> Steve
>
Quoted reply history
> -----Original Message-----
> From: [EMAIL PROTECTED] [mailto:[EMAIL PROTECTED]
> On Behalf Of Khaled Mohammed Abduljalil
> Sent: Wednesday, April 11, 2007 9:15 AM
> To: [email protected]
> Subject: [NMusers] Weibull distribution
>
> Dear NONMEM users,
>
> I have tried to study the pk profiles of a drug after
> multiple oral dosage regimen of 500mg every 12hr. The
> estimation process was well performed with the first dose
> (only) using Weibull function. but if i apply the same
> control file to the whole data (ie, single dose and
> multiple doses), it does not work any more. I can not
> detect my error. Could any one tell me where is it?
> neither first order nor Mich.-Menten models fitted the
> data like weibull model.
>
> thank you very much in advance for your response.
>
> sincerely yours
> Abduljalil
>
> $SUBROUTINES ADVAN6 TRANS1 TOL=3
> $MODEL
> COMP=(DEPOT,DEFDOSE)
> COMP=(CENTRAL,DEFOBS)
>
> $PK
> CL=THETA(1)*EXP(ETA(1))
> V=THETA(2)*EXP(ETA(2))
> BETA=THETA(3)*EXP(ETA(3))
> ALPHA=THETA(4)*EXP(ETA(4))
>
> K=CL/V
>
> S1=1
> S2=V
>
> $ERROR
> DEL=0
> IF(F.EQ.0) DEL=0.001
> W=F
> IPRED=F
> IRES=DV-IPRED
> IWRES=IRES/(W+DEL)
> Y=F+EPS(1)
>
> $DES
> DADT(1)=-A(1)*(BETA/ALPHA)*((TIME/ALPHA)**(BETA-1))*EXP(-(TIME/ALPHA)**B
> ETA)
> DADT(2)=-DADT(1)-A(2)*K
>
> $THETA
> (0.01,17,80);
> (10,115,900);
> (0.1,2.2,30)
> (0.1,2.6,30)
> (0.001,2)
> (0.001,1)
>
> $OMEGA
> 0.1 0.2 0.08 0.2
>
> $SIGMA
> 0.2
>
> $EST METHOD=1 INTER PRINT=5 NOABORT MAXEVAL=9999
> ************************************************************
> The contents of this message are intended only for the use
> of the individual to which they are addressed and may
> contain confidential or privileged information. If you are
> not the intended recipient, you are hereby notified that
> any use, distribution, disclosure or copying of this
> message, any attachment or the information contained
> therein is strictly prohibited. If you have received this
> transmission in error, please notify the original sender
> immediately and delete all copies of this message, along
> with any attachments. Thank you.
> ************************************************************
--
Nick Holford, Dept Pharmacology & Clinical Pharmacology
University of Auckland, 85 Park Rd, Private Bag 92019, Auckland, New Zealand
email:[EMAIL PROTECTED] tel:+64(9)373-7599x86730 fax:373-7556
http://www.health.auckland.ac.nz/pharmacology/staff/nholford/